title: Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SOD1 gene.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease caused by the selective death of motor neurons. Between 5% and 10% of ALS patients have a genetically inherited form of the disease known as familial ALS (FALS), and approximately 20% of FALS patients have mutations in the SOD1 gene. Although the mechanism underlying motor neuron death has not yet been fully clarified, it is supposed to be not completely consistent with apoptosis, necrosis, or autophagic cell death. Recently, it was found that general transcriptional repression induces slowly progressive atypical cell death associated with the shift of balance between YAPdeltaCs as prosurvival factors and activated p73 promoting apoptosis. This type of neuronal death was named transcriptional repression-induced atypical death (TRIAD). Therefore, to investigate possible relationships between the mechanism of motor neuron death in ALS and TRIAD, G93ASOD1 transgenic mice (Tg) were examined as an ALS model. The levels of YAPdeltaCs in the spinal cords of Tg mice decreased with disease progression, even during the presymptomatic stage, whereas FL-YAP, a p73 cofactor that promotes apoptosis, was preserved until the late symptomatic stage. Although the expression of total p73 also decreased with age in Tg mice, the ratio of phosphorylated p73 to total p73 increased during the late symptomatic stage in Tg mice. These results suggest that the progressive decrease in the levels of YAPdeltaCs and the relative increase in phosphorylation of p73 over the time course are correlated with disease progression in ALS model animals.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, 2-5-1 Shikata-cho, Okayama, Japan.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Nagai
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takehisa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazawa
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000375:Aging; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C000606290:SOD1 protein, human; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1